Abstract Hypertension (HT) in the general population is misdiagnosed by the use of clinic blood pressures (BP) alone. Some pafients have white coat hypertension (WCHT), while others have masked hypertension (MHT; normal clinic BP, but elevated daytime ambulatory BP). Ambulatory BP monitoring (ABPM) is required to correcfiy detect both WCHT and MHT. However, ABPM is costly, complex, and often unavailable for routine use in the esfirnated 65-70 million U.S. adults with pre-hypertension. We will therefore compare 4 methods ofBP measurement currently recommended for clinical practice: two occur in the clinic setting: routine CBP and automated CBP; two during daily life away from the clinic: ambulatory and home BP monitoring; we will test which best identifies those with MHT and WCHT. The study will recruit 300 subjects (men and women, aged 18-70, over-sampling those with elevated, untreated clinic BP) who will get all the BP measurements. CBP (convenfional and using the machine BpTRU) will be measured on 4 visits; Home BP will be measured with 3 readings (morning and evening) for 3 weeks; and Ambulatory BP will be measured twice with concurrent acfigraphy monitoring. Sociodemographic data, health and health behaviors, and anxiety will be assessed by questionnaire. Target organ damage will be assessed by arterial pulse wave recording (pulse wave velocity and augmentation index) and microalbuminuria. Blood will be drawn for metabolic and lipid profiling and genefic analysis. Data analyses will evaluate the reproducibility of the 4 methods, and their sensifivity and specificity for diagnosing HT, where an average daytime BP>135/85 mmHg is treated as the gold standard for this diagnosis. Aim 1 examines differences in the accuracy of diagnoses based on the different BP assessment methods, and differences in their strength of associafion with TOD and cardiovascular risk. For Aim 2, we will develop stepped algorithms for diagnosing HT at pre-specified levels of confidence and estimate their projected accuracy in the general population. Aim 3 will evaluate the short- and long-term cost-effectiveness of the individual methods and developed algorithms. The long-term goal of Project 3 is to improve the detection of HT, including those with MHT, so that treatment decisions are better informed, progression of TOD is slowed, and cardiovascular risk reduced. We believe that the results of this diagnosfic research will substanfially impact future guidelines for the assessment of HT, and facilitate the design of studies to evaluate the benefits of antihypertensive treatment in those with MHT.